65 results about "Hydrolase inhibitor" patented technology

The invention discloses methods of using cis-epoxyeicosantrienoic acids (“EETs”), inhibitors of soluble epoxide hydrolase (“sEH”), or a combination of an EET and an inhibitor of sEH, to reduce or prevent niacin-induced cutaneous vasodilation (“flushing”) in subjects suffering from this undesirable side effect of receiving therapeutic amounts of niacin.

The present invention is directed to methods for screening for metallohydrolase inhibitors using metal binding moieties in combination with targeting moieties.

Treatment with a cyclooxygenase-2 inhibitor and a leukotriene A4 hydrolase inhibitor is described as being useful in reducing recipient rejection of transplanted organs and for treatment of autoimmune diseases.

It has now been discovered that inhibitors of soluble epoxide hydrolase (“sEH”) are useful in reducing the severity of or inhibiting the progression of obstructive pulmonary diseases, restrictive airway diseases, and asthma. Administering a cis-epoxyeicosantrienoic acid (“EET”) in addition to the inhibitor is at least additive, and may be synergistic, in reducing or inhibiting these conditions and diseases, as measured by reduced numbers of neutrophils present in the lung. The inhibitor of sEH may be a nucleic acid, such as a small interfering RNA.

The release by trichomonads of a hydrolase that hydrolyzes a narrowly defined class of substrates at a low pH without interference from hydrolases that are unrelated to trichomoniasis is the basis for a selective diagnostic assay for trichomoniasis that measures hydrolysis of any of these substrates by vaginal fluid at a low pH. Selective assays for trichomoniasis are also obtained by removing particulate matter from a sample of vaginal fluid to extract a fraction devoid of particles greater than a selected size, and where desired, combining the extracted fraction with any of certain specified hydrolase inhibitors, then testing the fraction for enzymatic hydrolase activity. These qualities of trichomoniasis are the basis for a series of diagnostic tests and test devices that produce results that are detectable by visual and other means with a high degree of accuracy.

The present invention describes novel nitrosated and / or nitrosylated cyclooxygenase 2 (COX-2) inhibitors and novel compositions comprising at least one nitrosated and / or nitrosylated cyclooxygenase 2 (COX-2) inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and / or optionally, at least one therapeutic agent, such as, steroids, nonsteroidal antiinflammatory compounds (NSAID), 5-lipoxygenase (5-LO) inhibitors, leukotriene B4 (LTB4) receptor antagonists, leukotriene A4 (LTA4) hydrolase inhibitors, 5-HT agonists, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitors, H2antagonists, antineoplastic agents, antiplatelet agents, decongestants, diuretics, sedating or non-sedating anti-histamines, inducible nitric oxide synthase inhibitors, opioids, analgesics, Helicobacter pylori inhibitors, proton pump inhibitors, isoprostane inhibitors, and mixtures thereof. The present invention also provides novel compositions comprising at least one parent COX-2 inhibitor and at least one nitric oxide donor, and, optionally, at least one therapeutic agent. The present invention also provides kits and methods for treating inflammation, pain and fever; for treating and / or improving the gastrointestinal properties of COX-2 inhibitors; for facilitating wound healing; for treating and / or preventing renal toxicity; and for treating and / or preventing other disorders resulting from elevated levels of cyclooxygenase-2.

The invention describes novel substituted aryl compounds that are cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions comprising at least one cyclooxygenase 2 (COX-2) selective inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and / or, optionally, at least one therapeutic agent, such as, steroids, nonsterodal anti-inflammatory compounds (NSAID), 5-lipoxygenase (5-LO) inhibitors, leukotriene B4 (LTB4) receptor antagonists, leukotriene A4 (LTA4) hydrolase inhibitors, 5-HT agonists, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitors, H2 antagonists, antineoplastic agents, antiplatelet agents, thrombin inhibitors, thromboxane inhibitors, decongestants, diuretics, sedating or non-sedating anti-histamines, inducible nitric oxide synthase inhibitors, opioids, analgesics, Helicobacter pylori inhibitors, proton-pump-inhibitors, isoprostane inhibitors, and mixtures thereof. The invention also provides novel kits comprising at least one COX-2 selective inhibitor, and, optionally, at least one nitric oxide donor, and / or, optionally, at least one therapeutic agent. The novel cyclooxygenase 2 selective inhibitors of the invention can be optionally nitrosated and / or nitrosylated. The invention also provides methods for treating inflammation, pain and fever; for treating and / or improving the gastrointestinal properties of COX-2 selective inhibitors; for facilitating wound healing; for treating and / or preventing renal toxicity or other toxicities; for treating and / or preventing other disorders resulting from elevated levels of cyclooxygenase-2; and for improving the cardiovascular profile of COX-2 selective inhibitors.

The invention provides mature peptide of a myotis brandti leukotriene A4 hydrolase inhibitor Motistin and an application of the mature peptide, and belongs to the technical field of biological medicine. The amino acid sequence of the mature peptide is shown as SEQ ID NO: 2. The invention discovers for the first time that the mature peptide of Motistin can inhibit the hydrolase activity of LTA4H without affecting the aminopeptidase activity of LTA4H. The mature peptide of Motistin can target LT44H, can inhibit the recruitment of immune cells and the generation of inflammatory mediators by inhibiting the hydrolase activity of LTA4H, and also has the function of inhibiting the generation of inflammatory cytokines IL6, TNF <alpha> and IL1<beta> caused by virus and bacterial lipopolysaccharide.The mature peptide has the potential of becoming an effective drug for inhibiting inflammation.

Described herein is a method for determining an effective dose of a composition for inhibiting fatty acid amide hydrolase activity in vivo, by first administering to a subject a dose of a test composition, and subsequently assessing if the level of a fatty acid amide in the subject increases. Also described, is a method for optimizing therapeutic efficacy for treatment of anxiety, depression, pain, or a metabolic disorder by increasing or decreasing a dose of a fatty amide hydrolase inhibitor according to a patient's fatty acid amide levels. In addition, pharmaceutical compositions are described, which contain fatty acid amide hydrolase inhibitors effective for increasing a FAA level in a patient.

The invention discloses an application of chiral chloroquine, hydroxychloroquine or pharmaceutically acceptable salts of the chiral chloroquine and hydroxychloroquine in preparation of drugs used forpreventing and / or treating coronavirus pneumonia by using a coronavirus key drug target 3CL hydrolase (Mpro) as an action target. The chiral chloroquine and hydroxychloroquine have high bonding strength with the Mpro causing inflammation of the lung and the like; the activity of the Mpro can be significantly inhibited; and the chiral chloroquine and hydroxychloroquine are indicated to have the effect of preventing and treating pneumonia caused by coronaviruses and be able to be used as anti-pneumonia drugs. Through evaluation on the inhibitory activity of an hERG potassium ion channel, the concentration at which the chloroquine, hydroxychloroquine and enantiomers of the chloroquine and hydroxychloroquine are likely to generate cardiotoxicity to the hERG potassium ion channel is provided. The chiral chloroquine and hydroxychloroquine are prepared through chiral high-performance liquid chromatography and chiral synthesis; S-configuration chloroquine, hydroxychloroquine or salts of the chloroquine and hydroxychloroquine can be selected as a drug independently, or form a pharmaceutical composition for treating diseases caused by the coronaviruses; and due to higher activity and low cardiotoxicity of the chloroquine, hydroxychloroquine or salts of the chloroquine and hydroxychloroquine, the administration dosage range is greatly widened.

Belonging to the field of the research and development of microbial medicines, the present invention relates to a preparation method for extracting a novel glycoside hydrolase inhibitor from the fermentation liquor of Streptomyces globisporus. The method has the following characteristics: the fermentation liquor of Streptomyces globisporus is sterilized with high temperature, ultrafiltered and nanofiltered; the concentrated solution is absorbed and eluted by macroporous absorption resin; and after depressurization and concentration, the active component is frozen and dried, so that the glycoside hydrolase inhibitor is prepared. The method has the following advantages: the extraction technique is simple; the extraction process does not need acid and alkali; environment can be protected; and moreover, the extracted glycoside hydrolase inhibitor has inhibition activity on both pancreatic Alpha-amylase and Alpha-glucosaccharase and can be used for the development of blood sugar-decreasing products and weight-losing products.

The invention relates to an activity detection method of ester type catechin synthetase. The method comprises five steps, namely preparation of enzyme solution, preparation of reaction solution, preparation of contrast solution, detection of enzyme activity, and calculation of the enzyme activity. The ester type catechin serving as an enzyme reaction product is detected by using high performance liquid chromatography so as to detect the enzyme activity, and interference of oxidase and ester type catechin hydrolase on enzyme activity detection can be avoided by adding antioxidant and hydrolaseinhibitor in the reaction system can be avoided. The method is simple, has strong accuracy and high sensitivity, and can accurately detect the reaction product of the ester type catechin synthetase; and the operation is convenient, the detection time is short, fussy experiment operation is avoided, and the detection can be finished in 2 to 3 hours.

The present invention provides process of preparing orally taken preparations with blood sugar reducing active polypeptide component extracted from cucurbit plant. The blood sugar reducing active polypeptide component and protein hydrolase inhibitor extracted separately or simultaneously from cucurbit plant are cooled, dried, mixed in certain ratio while adding proper amount of supplementary material, and further treated to produce capsule, tablet, granule or buccal tablet for treating type I and type II diabetes. The blood sugar reducing active polypeptide component is prepared with cucurbit plant material and through crushing, homogenating, extracting, filtering, column chromatography, cooling, drying and other steps.

This invention belongs to screening model of enzyme inhibitor. adenosine homocysteine is a significant target enzyme, anti- inflammation, anti- virus, anti- tumor, cure cardiovascular disease. We can cure different disease when we adjust enzyme activity. This invention aims to search for a inhibitor and new medicine valuable. Use the basic material of adenosine homocysteine and activated agar gelatin, through the way of coupling, obtain immobilized enzyme, add oxygenation enzyme I (NAD+) to hold the its activity. Its high quantity screening of the inhibitor especially used to colored compound, and complex composition e.g. Chinese traditional medicine and extraction of inartificial plants.

The present invention is directed to AHCY inhibitors of formula (I): which are useful in the treatment of diseases characterized by high homocysteine levels, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases characterized by high homocysteine levels.

An adenosine homotype of cysteine hydrolase depressant, 9-[(1'R, 2', S, 3'R)-2',3'-dihydroxycyclopentyl] adenine (DHCaA), 9-(trans-2', trans-3'-dihydroxycyclopentyl-4'-enylester) adenine (DHCeA) and its 3-site nitrogen analog is disclosed. It can be used to treat lupus erythematosus and allergic dermatitis.

The invention discloses a medical composition having maltose hydrolase inhibitory activity, and an application of the medical composition. The medical composition having maltose hydrolase inhibitory activity comprises a flavonoid compound and 1-deoxynojirimycin, wherein the flavonoid compound is selected from at least one of monomers, organic salts of the monomers, or inorganic salts of the monomers: baicalein, wild baicalein and quercetagetin. The medical composition disclosed by the invention can effectively reduce postprandial blood sugar, can restrain the activity of maltose hydrolase using maltose as a substrate, and less uses maltose hydrolase inhibitors, so that medicine effects can be increased; and the medical composition is a natural product active component, is low in side effects, can reduce the postprandial blood sugar and can prevent or treat diabetes.

The invention discloses a method for synthesizing 4-amino-2-chlorine-3-nitro pyridine. The method comprises the following steps: adopting 65% nitric acid and concentrated sulfuric acid as mixed acid for nitratlon reaction, wherein the yield of the prepared isomer 4-amino-chlorine-3-nitro pyridine and 4-amino-2-chlorine-5-nitro pyridine is 95 to 98%, the purity is 95 to 99.5%, and subsequently purifying through recrystallization, effectively separating the prepared 4-amino-2-chlorine-3-nitro pyridine and 4-amino-2-chlorine-5-nitro pyridine, wherein the yield of the prepared 4-amino-2-chlorine-3-nitro pyridine is 75 to 85%, the purity of the prepared 4-amino-2-chlorine-3-nitro pyridine is 95 to 99%, the yield of the prepared 4-amino-2-chlorine-5-nitro pyridine is 15 to 25%, and the purity of the prepared 4-amino-2-chlorine-5-nitro pyridine is 95 to 99%. The method is applicable to preparation of 4-amino-2-chlorine-3-nitro pyridine and 4-amino-2-chlorine-5-nitro pyridine, and medicines such as an E1 active enzyme inhibitor, an adenosine homocysteine hydrolase inhibitor, a PLK1 recombinant protein inhibitor and benzimidazole can be further prepared.

The present invention relates to O-GlcNAc hydrolase (OGA) inhibitors. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which inhibition of OGA is beneficial, such as tauopathies, in particular Alzheimer's disease or progressive supranuclear palsy; and neurodegenerative diseases accompanied by a tau pathology, in particular amyotrophic lateral sclerosis or frontotemporal lobe dementia caused by C9ORF72 mutations.

The present invention relates to O-GlcNAc hydrolase (OGA) inhibitors. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which inhibition of OGA is beneficial, such as tauopathies, in particular Alzheimer's disease or progressive supranuclear palsy; and neurodegenerative diseases accompanied by a tau pathology, in particular amyotrophic lateral sclerosis or frontotemporal lobe dementia caused by C9ORF72 mutations.

Disclosed is a nanobody preparation system for administration through the internal and external epidermis of head and neck and internal epidermal layer of nasal cavity, comprising a specific nanobody having a biological activity and an antibody-drug carrier for improving the stability and tissue penetration of the nanobody. The drug carrier comprises one or more of a water-soluble macromolecular bio-saccharide gum substrate, polyvinyl alcohol, polyamino acid, glycerine, phospholipid, sodium carboxymethyl cellulose, collagen, and a hydrolase inhibitor.

The invention provides an ursolic acid neutral cholesterol ester hydrolase inhibitor and application thereof and belongs to the technical field of biological medicines. The ursolic acid compound can strongly and selectively inhibit activity of NCEH1, and further oral bioavailability of a carboxylic ester exogenous precursor medicine is improved. The inhibitor can inhibit clopidogrel from metabolizing a non-active product and can be taken as a clopidogrel synergist. The inhibitor also can alleviate lipid ectopic deposition-induced insulin resistance and even impaired glucose tolerance by inhibiting NCEH1 from participating in fat metabolism. In vitro activity determination finds that the compound (3-hydropropionyl-ursolic acid) has the NCEH1 inhibition IC50 reaching 12 nanomole, and anotherhuman body carboxylesterase (hCE2) is not obviously inhibited, so that selectivity reaches up to 6919 times. Besides, the compound also has the advantages of good safety, simple preparation technology and high synthesis yield, so that the compound has a good application prospect.

The present invention relates to O-GIcNAc hydrolase (OGA) inhibitors of formula (I). The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparingsuch compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which inhibition of OGA is beneficial, such as tauopathies in particular Alzheimer's disease or progressive supranuclear palsy; and neurodegenerative diseases accompanied by a tau pathology, in particular amyotrophic lateral sclerosis or frontotemporal lobe dementiacaused by C90RF72 mutations.

The present invention provides conjugates comprising a substituted aminopyridine covalently attached to an organic molecule via an amide bond. Such conjugates find utility as substrates for amide hydrolases, where the substituted aminopyridine acts as a fluorescent reporter of amide hydrolase activity. As a result, the conjugates described herein can advantageously be used in assays to detect amide hydrolase activity based upon measuring the fluorescence of a substituted aminopyridine that is released after amide hydrolysis. The conjugates of the present invention are also particularly useful in screening assays, which enable the identification of inhibitory molecules for amide hydrolases and other enzymes. The identified amide hydrolase inhibitors can be used in the treatment of a variety of diseases and disorders associated with aberrant amide hydrolase activity.

The present invention relates to O-GIcNAc hydrolase (OGA) inhibitors having the structure shown in formula (I). The invention is also directed to pharmaceutical compositions comprising such compoundsto processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which inhibition of OGA is beneficial, such as tauopathies, in particular Alzheimer's disease or progressive supranuclear palsy; and neurodegenerative diseases accompanied by a tau pathology, in particular amyotrophic lateral sclerosis or frontotemporal lobe dementia caused by C90RF72 mutations. wherein RB is an aromatic heterobicyclic radical selected from the group consisting of (b-1) to (b-6).

The present invention concerns a method for selectively activating a thermostable hydrolase at a temperature above T1. The present invention provides compositions comprising a thermostable hydrolase and a temperature sensitive inhibitor, wherein said thermostable hydrolase and said temperature sensitive inhibitor form a hydrolase-inhibitor complex at a temperature below T1, but which dissociates at a temperature of about T1. The present invention also relates to uses of said compositions, and a method for preparing said compositions.

The present invention provides a method of treating a patient suffering from pain or other FAAH mediated conditions by administering a fatty acid amide inhibiting amount of a compound represented by the formula:wherein R1 is H;R2 is a radical selected from the group consisting of H, hydrocarbyl and substituted hydrocarbyl;R3 is a radical selected from the group consisting of H, hydrocarbyl and substituted hydrocarbyl;X is CHCH, (CH2)n or O(CH2)n, wherein n is 0 or an integer of from 1 to 4; andW is O, S, or NR6, wherein R6 is selected from the group consisting of H and alkyl.

The invention discloses a method for synthesizing 4-amino-2-chlorine-3-nitro pyridine. The method comprises the following steps: adopting 65% nitric acid and concentrated sulfuric acid as mixed acid for nitratlon reaction, wherein the yield of the prepared isomer 4-amino-chlorine-3-nitro pyridine and 4-amino-2-chlorine-5-nitro pyridine is 95 to 98%, the purity is 95 to 99.5%, and subsequently purifying through recrystallization, effectively separating the prepared 4-amino-2-chlorine-3-nitro pyridine and 4-amino-2-chlorine-5-nitro pyridine, wherein the yield of the prepared 4-amino-2-chlorine-3-nitro pyridine is 75 to 85%, the purity of the prepared 4-amino-2-chlorine-3-nitro pyridine is 95 to 99%, the yield of the prepared 4-amino-2-chlorine-5-nitro pyridine is 15 to 25%, and the purity of the prepared 4-amino-2-chlorine-5-nitro pyridine is 95 to 99%. The method is applicable to preparation of 4-amino-2-chlorine-3-nitro pyridine and 4-amino-2-chlorine-5-nitro pyridine, and medicines such as an E1 active enzyme inhibitor, an adenosine homocysteine hydrolase inhibitor, a PLK1 recombinant protein inhibitor and benzimidazole can be further prepared.